title: Regulation of cytochrome P450 1B1 expression by luteinizing hormone in mouse MA-10 and rat R2C Leydig cells: role of protein kinase A.
abstract: In the present study, we investigated the signaling pathway involved in luteinizing hormone (LH)-mediated regulation of testicular CYP1B1 in mouse MA-10 and rat R2C Leydig cells. CYP1B1 mRNA and protein levels were measured in MA-10 and R2C cells treated with LH and protein kinase activators or inhibitors. Treatment with LH or 8-bromo-cAMP, a protein kinase A (PRKA) activator, increased CYP1B1 expression and PRKA activity in a concentration-dependent manner in both cell lines, albeit to different extents. Treatment with 8-(4-chlorophenylthio)adenosine-3',5'-cyclic monophosphorothioate, Rp-isomer, a PRKA inhibitor, decreased basal CYP1B1 expression and attenuated LH-elicited increases in CYP1B1 mRNA and protein levels and PRKA activity. In contrast, treatment with a protein kinase G activator or an inhibitor of protein kinase C had no effect on basal or LH-induced CYP1B1 expression in MA-10 or R2C cells. Collectively, the results identify PRKA as the major signaling pathway involved in the LH-mediated regulation of testicular CYP1B1 expression in Leydig tumor cells.
authors.affiliation: Faculty of Pharmaceutical Sciences, The University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Subrata
authors.initials: S
authors.lastname: Deb
authors.forename: Stelvio M
authors.initials: SM
authors.lastname: Bandiera
mesh_terms: D000818:Animals; D001189:Aryl Hydrocarbon Hydroxylases / Q000378:metabolism*; D045744:Cell Line, Tumor; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D017869:Cyclic GMP-Dependent Protein Kinases / Q000378:metabolism; D065633:Cytochrome P-450 CYP1B1; D007985:Leydig Cells / Q000201:enzymology*; D007986:Luteinizing Hormone / Q000378:metabolism*; D008297:Male; D051379:Mice; D011493:Protein Kinase C / Q000378:metabolism; D051381:Rats; D011974:Receptors, LH / Q000378:metabolism*; D015398:Signal Transduction; D015854:Up-Regulation
chemical_list: D011974:Receptors, LH; D007986:Luteinizing Hormone; D001189:Aryl Hydrocarbon Hydroxylases; C585498:Cyp1b1 protein, mouse; C585499:Cyp1b1 protein, rat; D065633:Cytochrome P-450 CYP1B1; D017868:Cyclic AMP-Dependent Protein Kinases; D017869:Cyclic GMP-Dependent Protein Kinases; D011493:Protein Kinase C